Helmuth Margaret E, Smith Abigail R, Glaser Alexander P, Yang Claire C, Cameron Anne P, Henry Lai H, Griffith James W, Eric Jelovsek J, Quentin Clemens J, Helfand Brian T, Merion Robert M, Andreev Victor P
Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Northwestern Medicine, Feinberg School of Medicine, Chicago, Illinois, USA.
Neurourol Urodyn. 2025 Jan;44(1):178-193. doi: 10.1002/nau.25596. Epub 2024 Oct 7.
Men with lower urinary tract symptoms (LUTS) represent a heterogeneous group, and treatment decisions are often based on severity of symptoms and physical examination findings. Identification of clinically meaningful subtypes could allow for more personalized care. This study advances phenotyping efforts from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) by adding data domains to previous phenotyping using urologic symptoms alone.
Two-hundred-seventeen LUTS, demographics, medical history, and physical examination datapoints from the LURN Observational Cohort study were assessed among 519 men with at least one bothersome LUTS, using weighted Tanimoto indices, semi-supervised learning, and resampling-based consensus clustering to identify distinct clusters of participants. Differentially abundant serum proteins of 220 men were compared across identified clusters.
Five refined male clusters (RM1-RM5) were identified. Two clusters reported mild LUTS (RM1: n = 66; RM2: n = 84). RM1 was older than RM2 (70.3 vs. 56.1 years), had more comorbidities (functional comorbidity index 2.4 vs. 1.5) and erectile dysfunction. Two benign prostatic hyperplasia-like symptom clusters were identified (RM3: n = 64; RM4: n = 188). RM3 has the largest postvoid residual volume (275 mL); RM4 reported more urinary frequency, urgency, urinary incontinence, pain, and psychosocial symptoms. RM5 (n = 119) was characterized by urgency urinary incontinence, frequency, and significant comorbidities and psychosocial symptoms. Fifteen (RM2) to 87 (RM1) differentially abundant proteins were identified within each cluster. Minimal overlap was observed between affected proteins and pathways across clusters.
Protein signatures across newly discovered subgroups suggest identified subtypes are biochemically distinct. Findings should be validated, but may represent populations with separate pathophysiology and therapeutic needs.
The LURN ClinicalTrials.gov Identifier is NCT02485808.
患有下尿路症状（LUTS）的男性是一个异质性群体，治疗决策通常基于症状的严重程度和体格检查结果。识别具有临床意义的亚型有助于实现更个性化的治疗。本研究通过在先前仅使用泌尿系统症状进行表型分析的基础上增加数据域，推进了下尿路功能障碍症状研究网络（LURN）的表型分析工作。
在519名至少有一种困扰性LUTS的男性中，评估了来自LURN观察性队列研究的217个LUTS、人口统计学、病史和体格检查数据点，使用加权谷本指数、半监督学习和基于重采样的一致性聚类来识别不同的参与者集群。比较了220名男性在已识别集群中的差异丰富血清蛋白。
识别出五个细化的男性集群（RM1 - RM5）。两个集群报告有轻度LUTS（RM1：n = 66；RM2：n = 84）。RM1比RM2年龄更大（70.3岁对56.1岁），合并症更多（功能合并症指数2.4对1.5）且有勃起功能障碍。识别出两个良性前列腺增生样症状集群（RM3：n = 64；RM4：n = 188）。RM3的残余尿量最大（275 mL）；RM4报告有更多的尿频、尿急、尿失禁、疼痛和心理社会症状。RM5（n = 119）的特征是急迫性尿失禁、尿频以及显著的合并症和心理社会症状。每个集群中识别出15种（RM2）至87种（RM1）差异丰富的蛋白质。各集群中受影响的蛋白质和通路之间观察到最小程度的重叠。
新发现亚组中的蛋白质特征表明所识别的亚型在生物化学上是不同的。研究结果应进行验证，但可能代表具有不同病理生理学和治疗需求的人群。
LURN在ClinicalTrials.gov的标识符为NCT02485808。
